Mechanistic Insights in Glycation-Induced Protein Aggregation

Show simple item record Adrover Estelrich, Miguel Mariño Pérez, Laura Sanchís Cortés, María del Pilar Pauwels, K. Kraan, Y. Lebrun, P. Vilanova Canet, Bartolomé Muñoz Izquierdo, Francisco Broersen, K. Donoso Pardo, Josefa Laurentina 2018-11-21T12:41:28Z
dc.description.abstract [eng]Protein glycation causes loss-of-function through a process that has been associated with several diabetic-related diseases. Additionally, glycation has been hypothesized as a promoter of protein aggregation, which could explain the observed link between hyperglycaemia and the development of several aggregating diseases. Despite its relevance in a range of diseases, the mechanism through which glycation induces aggregation remains unknown. Here we describe the molecular basis of how glycation is linked to aggregation by applying a variety of complementary techniques to study the nonenzymatic glycation of hen lysozyme with ribose (ribosylation) as the reducing carbohydrate. Ribosylation involves a chemical multistep conversion that induces chemical modifications on lysine side chains without altering the protein structure, but changing the protein charge and enlarging its hydrophobic surface. These features trigger lysozyme native-like aggregation by forming small oligomers that evolve into bigger insoluble particles. Moreover, lysozyme incubated with ribose reduces the viability of SH-SY5Y neuroblastoma cells. Our new insights contribute toward a better understanding of the link between glycation and aggregation.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Biomacromolecules, 2014, vol. 15, p. 3449-3462
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title Mechanistic Insights in Glycation-Induced Protein Aggregation
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2018-11-21T12:41:28Z info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.subject.keywords Protein glycation
dc.subject.keywords advanced glycation end products
dc.subject.keywords lysozyme
dc.subject.keywords Estructura Biopolímers
dc.subject.keywords Agregación
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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